Dioctadecyldimethylammonium:Monoolein Nanocarriers for Efficient in Vitro Gene Silencing
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Data
2014-05-14
Autores
Norberto Oliveira, Ana Cristina
Martens, Thomas Frans
Raemdonck, Koen
Adati, Renata Danielle [UNESP]
Feitosa, Eloi [UNESP]
Botelho, Claudia
Gomes, Andreia Castro
Braeckmans, Kevin
Dias Real Oliveira, Maria Elisabete Cunha
Título da Revista
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Título de Volume
Editor
Amer Chemical Soc
Resumo
This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid mono olein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.
Descrição
Palavras-chave
counterion, gene silencing, Liposomes, Monoolein, siRNA delivery
Como citar
Acs Applied Materials & Interfaces. Washington: Amer Chemical Soc, v. 6, n. 9, p. 6977-6989, 2014.